Relaxation of cat tracheobronchial and pulmonary arterial smooth muscle by vasoactive intestinal peptide: lack of influence by peptidase inhibitors

Altiere, Ralph J.; Diamond, Louis K.

doi:10.1111/j.1476-5381.1984.tb10766.x

Cited by 35 publications

(15 citation statements)

References 21 publications

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“…However, it is unlikely that an opioid peptide is involved, since the NANC response is unaffected by naloxone (Ellis & Farmer, 1989). Our results agree with those obtained with cat trachea (Altiere & Diamond, 1984), in that, in guinea-pig trachea, enzymatic inactivation of VIP does not seem to be an important mechanism. If VIP or PHI do play a role as NANC transmitters in the lung, they may be removed by the circulation and metabolized by blood-borne peptidases.…”

Section: Resultssupporting

confidence: 82%

“…Effects of a-chymotrypsin were prevented completely by preincubation with aprotinin (1.75umlP1; Figures 2 and 3). In the presence of occhymotrypsin, responses to both VIP and PHI, even achea, whereas responses to VIP are abol--chymotrypsin (Altiere & Diamond, 1984), " inhibitory response is unaffected (Altiere id, 1985). This suggested firstly, that VIP, (Matsuzaki et al, 1980;Ellis & Farmer, 1989).…”

Section: Resultsmentioning

confidence: 99%

“…VIP is a potent relaxant of guinea-pig (Venugopalan et al, 1986) and feline (Altiere & Diamond, 1984) airway smooth muscle in vitro. The latter study demonstrated that preincubation of cat trachea with the peptidase enzyme a-chymotrypsin abolished the effect of exogenous VIP.…”

Section: Introductionmentioning

confidence: 99%

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Effects of peptidases on non‐adrenergic, non‐cholinergic inhibitory responses of tracheal smooth muscle: a comparison with effects on VIP‐ and PHI‐induced relaxation

Ellis

Farmer

1989

British J Pharmacology

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1 The effects of peptidase enzymes on non-adrenergic, non-cholinergic (NANC) inhibitory responses of guinea-pig trachea to electrical field stimulation (EFS), and on relaxations induced by vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) have been examined. 2 a-Chymotrypsin reduced both the magnitude and, particularly, the duration of the inhibitory response to EFS, whereas papain reduced only the magnitude. Aprotinin, a peptidase inhibitor prevented the effects of a-chymotrypsin but was without effect on papain. 3 a-Chymotrypsin and papain both abolished relaxant responses to exogenous VIP and PHI. The action of a-chymotrypsin was prevented by aprotinin, whereas that of papain was not affected. 4 The peptidases were without effect on concentration-response curves to methacholine or to isoprenaline. It was also observed that, in the absence of the peptidases, aprotinin had no effect on inhibitory responses either to EFS or to exogenous VIP and PHI. 5 It is suggested that neuropeptides, possibly VIP and PHI, released during EFS of guinea-pig trachea, partly mediate NANC relaxations, and that their action may be inhibited by peptidases. However, the lack of effect of aprotonin alone, on responses to EFS, suggests that, if endogenous peptidases are important in terminating the action of neuropeptides, they are resistant to the effect of this particular peptidase inhibitor. It is further suggested that neurogenic relaxation of guinea-pig trachea is also partly mediated by a substance, possibly non-peptide, other than VIP or PHI.

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

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Effects of peptidases on non‐adrenergic, non‐cholinergic inhibitory responses of tracheal smooth muscle: a comparison with effects on VIP‐ and PHI‐induced relaxation

Ellis

Farmer

1989

British J Pharmacology

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“…The substantial remainder of α-chymotrypsin-and VIP-antagonist-resistant and L-NAME-insensitive NANC relaxation was suppressed by tetrodotoxin. Furthermore, the overall conclusion of earlier works concerning the effects of α-chymotrypsin on exogenously applied VIP or NANC relaxation, seems to be that VIP is not involved in the NANC relaxation [22]. These observations may also indicate that neurotransmitters other than VIP and NO are involved in the NANC inhibitory neurotransmission in the airway.…”

Section: Discussionsupporting

confidence: 48%

L-NAME-sensitive and -insensitive nonadrenergic noncholinergic relaxation of cat airway in vivo and in vitro

Aizawa

Tanaka²,

Sakai³

et al. 1997

Eur Respir J

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The neurotransmitters responsible for neurogenic airway relaxation are still unknown. We investigated the effects of N ω -nitro-L-arginine methylester (L-NAME) on nonadrenergic and noncholinergic (NANC) relaxation evoked by electrical stimulation of vagus nerves in vivo and in vitro in cat.To that end, we measured pulmonary resistance during vagal nerve stimulation (VS) in vivo, and isometric tension of small bronchi (1-3 mm outer diameter) during electrical field stimulation (EFS) in vitro. During infusion of 5-hydroxytryptamine (5-HT), VS transiently decreased total pulmonary resistance in the presence of atropine and propranolol, with peak relaxation at several seconds after the VS and a gradual return to baseline within 2-3 min. L-NAME abolished the initial peak relaxation and reduced the peak amplitude, but did not affect the duration of the NANC relaxation. In small bronchi obtained from control cats, EFS evoked a biphasic NANC relaxation, comprising an initial fast component followed by a second slow component, and L-NAME (10 -5 M) selectively abolished the first component without affecting the second. Whilst in the small bronchi obtained from L-NAME pretreated cats, EFS elicited only the slow component of NANC relaxation, which was insensitive to L-NAME but sensitive to tetrodotoxin.These results indicate that nonadrenergic noncholinergic relaxation induced by vagal nerve stimulation during infusion of 5-hydroxytryptamine can be classified into two components, and that at least two neurotransmitters, including nitric oxide, are involved in the relaxation. Eur Respir J 1997; 10: 314- Neurally-mediated relaxation of airway smooth muscle in various animal species, including man, is largely nonadrenergic and noncholinergic (NANC) (see, for example, [1]). Although the neurotransmitter(s) responsible for NANC relaxation in the airways have not been conclusively identified, nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) have emerged as strong candidates [2][3][4][5][6][7].In cat airway, we have shown that NANC relaxation can be classified into two components by thresholds for activation or by sensitivity to N ω -nitro-L-arginine methylester (L-NAME), and that the pattern of L-NAME-sensitive and -insensitive components differs in central and peripheral airways [6,7]. Specifically, electrical field stimulation (EFS) elicited monophasic relaxation in the trachea, confirming previous observations [5,8], but biphasic NANC relaxations, comprising an initial fast component followed by a second slow component in the bronchioles. L-NAME selectively abolished the first component of NANC relaxation without affecting the second in bronchioles, whilst, in the trachea, L-NAME completely suppressed the monophasic NANC relaxation after single or short repetitions (<5) of 1 ms pulse stimuli; however, after more stimuli (>10) of 1 or 4 ms duration, suppression of NANC relaxation was incomplete (to 40-50% of the control value) [7]. VIP antagonists partially suppressed the L-NAME-resistant NANC relaxation....

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“…Further, in feline airways in vitro aprotinin Lions with intact epithelium, but had no and captopril have no effect on VIP-induced relaxation achea ( Figure 6). The pD2 value for intact (Altiere & Diamond, 1984). Previous studies in our laboratory nce of thiorphan, was 8.07 + 0.10 and this also showed that aprotinin had no effect on responses of rom the value of 8.30 + 0.08 in denuded guinea-pig trachea, either to exogenous VIP or to NANC ro2.3, n = 7).…”

Section: Effects Ofpeptidase Inhibitorssupporting

confidence: 57%

Effects of epithelium removal on relaxation of airway smooth muscle induced by vasoactive intestinal peptide and electrical field stimulation

Farmer

Togo

1990

British J Pharmacology

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1 We have studied the effect of epithelium removal on relaxation of guinea-pig isolated tracheal smooth muscle induced by vasoactive intestinal peptide (VIP) or stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves. Also examined were the effects of inhibitors of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE).2 Epithelium removal produced a 3.6 + 0.4 fold leftward shift in the VIP concentration-response curve. The supersensitivity to VIP, following epithelium removal was abolished by phosphoramidon or thiorphan (NEP inhibitors), but unaffected by captopril (an ACE inhibitor). In intact trachea, the NEP inhibitors produced leftward shifts in the VIP curves similar to those produced by epithelium removal.3 In contrast to responses to exogenous VIP, neurogenic NANC inhibitory responses to electrical field stimulation were affected neither by epithelial denudation nor by the peptidase inhibitors. 4 As in previous studies, epithelium removal increased tracheal sensitivity to isoprenaline. This was not altered by pretreatment with a cocktail of peptidase inhibitors. Thus, the effect of the NEP inhibitors on responses to VIP appears to be relatively specific. 5 These data indicate that exogenous VIP is a substrate for airway NEP, since inhibition of the enzyme potentiates the peptide. This is further evidence that the airway epithelium provides a source for the metabolism of mediators.6 In guinea-pig trachea the NEP responsible for cleaving VIP may be located largely in the epithelial layer, since NEP inhibition was without effect on sensitivity to VIP in epithelium-denuded preparations. If VIP is a NANC inhibitory neurotransmitter in this tissue, its degradation endogenously does not appear to involve epithelial NEP.

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Relaxation of cat tracheobronchial and pulmonary arterial smooth muscle by vasoactive intestinal peptide: lack of influence by peptidase inhibitors

Cited by 35 publications

References 21 publications

Effects of peptidases on non‐adrenergic, non‐cholinergic inhibitory responses of tracheal smooth muscle: a comparison with effects on VIP‐ and PHI‐induced relaxation

Effects of peptidases on non‐adrenergic, non‐cholinergic inhibitory responses of tracheal smooth muscle: a comparison with effects on VIP‐ and PHI‐induced relaxation

L-NAME-sensitive and -insensitive nonadrenergic noncholinergic relaxation of cat airway in vivo and in vitro

Effects of epithelium removal on relaxation of airway smooth muscle induced by vasoactive intestinal peptide and electrical field stimulation

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